There are many diseases of the eyes or ocular diseases which affect vision. Some of these diseases include diseases of the conjunctive and cornea which can produce loss of visual acuity, pain and discharge, cataracts resulting in blurred vision, glare altered color perception and monocular diplopia, uveal diseases resulting in photophobia, ocular discomfort and visual blurring, retinal diseases resulting in distortion of straight lines (metamorphopsia), loss of central acuity and visual field abnormalities and diseases of Bruch's membrane, which may lead to age-related macular degeneration.
Among numerous forms of human retinopathies, age-related macular degeneration (hereinafter referred to as AMD) is the leading cause of severe vision loss in the elderly and affects between 6.4% (New Zealand)(19) and 6.9-11.4% (U.S.A.) (20, 21) of people beyond the age of 65. AMD is a heterogeneous group of retinal degenerations which is associated with alterations of retinal pigment epithelium (RPE) cells.
In the past transplantation of rod-enriched adult photoreceptor cell populations that may protect the macula from secondary degeneration in rod-cone retinitis pigmentosa affected patients was generally the therapy of choice for retinal degenerations, including AMD. However, the photoreceptors that were to be transplanted usually came from adult or embryonic human photoreceptors collected post-mortem. These photoreceptors can thus be infected by a diversity of viruses including the hepatitis virus, cytomegalovirus, and human immuno-deficiency virus as well as other pathogens such as prions that may remain undetectable prior to transplantation. Additionally, these cells may trigger a strong immune response in the host, leading to the destruction of the graft and/or inflammatory automimmune reactions.
Moreover, oculo gene therapy protocols which relied on the basis of cell transfection, viral cell infection, or cell transplantation were also known in this art. However one problem with the known gene therapy protocols was that adverse immunological side effects occurred. These adverse side effects, in some instances, could lead to anaphylactic shock, endangering the patient.
Among various protocols which have been designed to transfer therapeutically important genes to a target tissue, the transplantation of genetically engineered cells has become particularly promising in recent years. To protect allogeneic or xenogeneic grafts from immune rejection, cells have been successfully microencapsulated with non-degradable biocompatible polymers and used for the experiment treatment of several disorders as type I diabetes melitus (1-5), dwarfism (6), hemophilia B (7), anemia (8), chronic pain (9, 10), amyotrophic lateral sclerosis (11), as well as Parkinson's, Huntington's, and Alzheimer's diseases (12-18). However, none of these cited references taught a method for treating ocular diseases.
Thus, it is an object of the present invention to provide genetically modified cells which stably produce therapeutic factors suitable for treating ocular disorders.
It is another object of the present invention to provide methods of encapsulating such generally modified cells, in such a way that the cells remain viable and produce effective amounts of the biologically active agent(s) in the eye, more particularly in the retina.
It is another object of the present invention to provide a method for implanting in vivo these devices (encapsulated cells), and the effective release and treatment of ocular disorders in vivo.
It is another object of the present invention to provide ocular compositions that can be surgically retrieved from the ocular globes, for instance, in case of an occurrence of adverse side effects.
It is yet another object of the present invention to provide compositions and methods to deliver biologically active molecules to the eye to treat ocular disorders that and bacteriological and virological safe.
It is yet another object of the present invention to provide genetically engineered cell lines that can be systematically tested for any kind of pathogens before they are encapsulated and transplanted into human eyes.
It is yet another object of the present invention to provide a therapeutic method to promote the survival of photoreceptor cells in degenerating retinas of mammals in order to treat retinal degenerations, as well as treating mammals that have retinitis pigmentosa or age-related macular degeneration.
These and other objects are achieved by the present invention as evidenced by the summary of the invention, description of the preferred embodiments and the claims.